MicroRNAs as regulators of drug abuse and immunity

Abstract

MicroRNAs (miRNAs) are 20-22 nucleotide non-coding RNAs that participate in gene regulation. They bind to 3’-untranslated regions of their mRNA targets, inhibiting the transcripts’ translation and/or destabilizing them. Chronic drug abuse induces changes of miRNAs expression in the brain, which is thought to contribute to addictive behaviors. Lots of miRNAs have been identified to play critical roles in the development of drug addiction. Moreover, miRNAs have been shown to play critical roles in a broad array of biologic processes, including regulation of the cell cycle, oncogenic transformation, immune cell regeneration and differentiation, and psychiatry disorders. We hypothesized that chronic drug abuse leads to aberrant expression of several miRNAs, and then aberrant miRNAs influence the innate and adaptive immunity, especially differentiation and function of T cells and B cells, through down-regulated miRNAs’ target gene expression. Characterization of miRNA actions is important and has high potential effect for the management of drug addiction and immunity diseases. miRNAs are potential biomarkers, and the modulation of their expression can be used for therapeutic purposes.

Role of DNA Methyl-CpG-Binding Protein MeCP2 in Rett Syndrome Pathobiology and Mechanism of Disease

“…However, miR132 can fine-tune the MeCP2 level in the postnatal stages [ 222 ]. MeCP2 regulation by miR132 through binding to evolutionary conserved binding sites has been studied in animal models in different contexts from RTT [ 169 ] to drug abuse [ 223 ] and pain transmission [ 224 ]. However, the limited number of studies on human cells or brain samples is not consistent with the results from animal models [ 222 ].…”

Association of miR-155, miR-187 and Inflammatory Cytokines Il-10 and TNF-α in Chronic Opiate Abusers

“…IL-10 negatively regulates acute and chronic in ammation by blocking or reducing the output from immune cells of pro-in ammatory cytokines, including TNF-α, IL-6, and IL-12. [10] Since the amplitude and duration of the in ammatory response are regulated precisely by IL-10, we analysed the plasma levels of IL-10 at various doses of opium abuse and it was observed that there was a gradual but nonsigni cant increase in the plasma levels of IL-10 with increasing dose of opium (Table 2). Further, Rossato et al (2012) reported in an in vitro model, induction of the miR-187 in an IL-10 dependent manner, which further causes a transcriptional inhibition of mRNA of TNFα and IL-6 (via Ikβζ).…”

“…There are no studies exploring the roles of microRNA in opiate dependents, however, microarray analysis in varied drug addictions have revealed altered expression of miRNA regulating both innate and adaptive immune systems like miR-155, miR-187, miR-190, and miR184 [10]. Besides, Rossato et al (2012) [11] showed in human monocytes that miR187 is involved in the physiological regulation of IL-10-driven antiin ammatory responses and demonstrated miRNA-mediated strategies controlling cytokine expression in human monocytes activated by a TLR4 agonist (LPS).…”

Placental microRNA methylome signatures may serve as biomarkers and therapeutic targets for prenatally opioid-exposed infants with neonatal opioid withdrawal syndrome

“…There are many classes of ncRNAs, with a few functionally important types including microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA), piwi-interfering RNA (piRNA), and small nucleolar RNA (snoRNAs). Dysregulation of these ncRNAs is involved in many cancers and also drug abuse ( Zhang K. et al, 2016 ). MicroRNAs (miRNAs) are indeed one of the most prominent and extensively studied classes of non-coding RNAs (ncRNAs).…”